Search PubMed⌕ Search

Biomedical subjects

L M Pedersen

Publications and source records attributed to L M Pedersen.

At least 19 recordsLinked to original sources

Microalbuminuria is associated with impaired glomerular permselectivity in lymphoma patients.

Slightly increased urinary albumin excretion is frequently found in patients with lymphoma and other malignancies but the pathophysiological mechanisms have yet to be clarified. In this study, parameters of renal function in lymphoma patients with microalbuminuria were evaluated. Sixty-seven patients with histologically proven diffuse large B-cell lymphoma were included in the study at diagnosis. Urinary albumin excretion was measured by immunoturbidimetry and microalbuminuria was defined as an excretion rate between 20 and 200 microg/min. Glomerular function was further estimated by renal clearance of creatinine and IgG, and the IgG/IgG4 charge selectivity index. Tubular function was evaluated by renal clearance of beta(2)-microglobulin. The median value of IgG clearance was increased in the microalbuminuric patients (0.22 versus 0.18 microl/min; p = 0.03). The median selectivity index was significantly lower in patients with microalbuminuria (1.0 versus 2.2; p<0.0001). Urinary albumin excretion was correlated with both the renal clearance of IgG (p<0.0001) and the selectivity index (p<0.0001). These data suggest that a slightly elevated level of urinary albumin excretion in a population of patients with aggressive lymphoma reflects altered glomerular permselectivity probably due to a defect in charge selectivity. The glomerular sieving dysfunction may be associated with an inflammatory response to the malignancy. Further studies are needed to validate the clinical impact of the renal parameters in lymphoma patients.

Adult↗

Total and free insulin-like growth factor I, insulin-like growth factor binding protein 3 and acid-labile subunit reflect clinical activity in acromegaly.

The aim was to evaluate, markers of disease activity in acromegaly in relation to perceived disease activity. Thirty-seven consecutively treated, acromegalic patients, classified by clinical symptoms as inactive (n=16), slightly active (n=10) and active (n=11), entered the study. When evaluating the inactive and the active groups, we found that positive and negative predictive values (PV(pos), PV(neg)) for clinical disease activity of total and free insulin-like growth factor-I (IGF-I) were 0.59, 0.90 and 1.00, 0.82 respectively. Acid-labile subunit (ALS) showed diagnostic merit similar to insulin-like growth factor binding protein-3 (IGFBP-3) with PV(pos) of 0.69 and 0.71 and PV(neg) of 0.91 and 0.92 respectively. We conclude that free IGF-I is more closely related than total IGF-I to perceived disease activity and is as such useful when evaluating previously treated acromegaly for disease activity. Total IGF-I, IGFBP-3 and ALS possess a higher PV(neg) for the clinical disease activity. None of the parameters can at present be claimed to be superior to the others and thus all the measured parameters are recommended to be part of the evaluation of acromegalic patients.

Acromegaly↗

Production of hyaluronan and chondroitin sulphate proteoglycans from human arterial smooth muscle--the effect of glucose, insulin, IGF-I or growth hormone.

BACKGROUND: Although it is recognized that the extracellular matrix is important for cell proliferation, migration and metabolism of growth factors, the regulation of the synthesis of hyaluronan and chondroitin sulphate proteoglycan (CSPG) in the vessel wall is poorly understood. OBJECTIVE: To examine the role of glucose, insulin, IGF-I and human growth hormone (hGH) on the accumulation of hyaluronan and CSPG using cultures of human aortic smooth muscle cells. METHODS: The cultures were exposed for 36 h. The CSPG content in the incubation medium was measured by a combination of digestion with testicular hyaluronidase and precipitation of [35SO4(2-)]-labelled material with ethanol and trichloroacetic acid. Hyaluronan was estimated using a radiometric assay. RESULTS: Glucose and insulin reduced the amount of synthesized hyaluronan (2P<0.01). Stimulation of synthesis was seen with hGH (2P<0.01), whereas no effect was observed with IGF-I. The production of CSPG was increased with glucose and hGH (2P<0.01), but showed no change with insulin. CONCLUSIONS: The present data obtained with human arterial smooth muscle cells in vitro showed that glucose, insulin and hGH can influence the accumulation of hyaluronan and CSPG. These observations may be relevant for an understanding of diabetic macroangiopathy.

Adult↗

[Genital prolapse].

The prevalence of genital prolapse in women is unknown. The development of prolapse is dependent on the pelvic floor muscles and connective tissue. Risk factors are vaginal birth, obstipation, high abdominal pressure and surgical procedures. Preventive measures are discussed. The classification of prolapse is somewhat difficult. Conservative treatment with pessaries and pelvic floor muscle exercises and various surgical procedures are discussed.

Female↗

[The clinical impact of gestational diabetes mellitus].

In Denmark, gestational diabetes mellitus (GDM) develops in about 2% of all pregnant women. The discussion of GDM is complicated by lack of consensus regarding screening methods, diagnosis and treatment. Observational studies indicate that untreated GDM is associated with an increased risk of maternal and perinatal morbidity, and that the offspring of GDM mothers tend to be at increased risk of developing diabetes and adiposity as a result of an abnormal intrauterine environment. Several follow-up studies have shown that women with previous GDM run a considerable risk of developing diabetes (especially type 2 diabetes) later in life. Intervention strategies for this high risk group are suggested.

Diabetes, Gestational↗

Urinary albumin excretion and transcapillary escape rate of albumin in malignancies.

Transcapillary escape rate of albumin was determined in 22 patients with different malignancies. In addition, urinary albumin excretion rate was measured in 24-h urine samples using a sensitive immunoassay. Increased urinary albumin excretion was defined as >/=20 microg/min according to conventional standards. Renal glomerular filtration and tubular function was estimated by 51Cr-EDTA plasma clearance and urinary beta 2-microglobulin, respectively. Median urinary albumin excretion rate was 15.0 microg/min (range 6-510 microg/min) and the frequency of increased urinary albumin excretion was 41%. This agrees with other studies showing increased albuminuria in several types of malignant diseases. Patients with advanced disease (tumour, node, metastasis (TNM) stage II-IV) had a significantly higher urinary albumin excretion rate than patients with localized disease (TNM stage I). Serum creatinine, glomerular filtration rate and urinary beta 2-microglobulin were all within normal limits. Median transcapillary escape rate of albumin was 5.5 %/h (range 2-8 %/h) and this level is comparable with values in healthy subjects. There was no significant difference in transcapillary escape rate between patients with elevated urinary albumin excretion and the normoalbuminuric group. Median value of the absolut outflux of albumin was 10.6 g/h with similar levels in patients with increased urinary albumin excretion and patients with normoalbuminuria. Our results indicate a high prevalence of minor glomerular dysfunction with a slightly elevated urinary albumin excretion in patients with malignancies. The normal endothelial function, as estimated by the transcapillary escape rate of albumin, suggests an overall unaffected capillary permeability and increased urinary albumin loss appears to be an isolated renal phenomenon in cancer patients.

Adult↗

Sweat secretion rates in growth hormone disorders.

BACKGROUND: While increased sweating is a prominent symptom in patients with active acromegaly, reduced sweating is gaining status as part of the growth hormone deficiency (GHD) syndrome. DESIGN AND SUBJECTS: Sweat secretion rate (SSR), as measured by pilocarpine iontophoresis represents the maximal capacity for stimulated sweat secretion in a localized skin area. SSR was studied in 37 patients with a history of acromegaly, 20 adult patients with GHD before and during long-term GH substitution of GHD adults, and 58 control subjects. RESULTS: Acromegaly: Patients with acromegaly had significantly higher SSR than healthy controls (Z-score + 1.9 (+/- 1.1) mean (+/- SD) (P < 0.001)). SSR was increased irrespective of current clinical disease activity. Thus, the SSR Z-scores in 16 clinically inactive patients were + 2.1 (+/- 1.2), in 10 slightly or doubtfully active patients + 1.5 (+/- 0.7) and in 11 active patients + 1.8 (+/- 1.3). There was no correlation between SSR and IGF-I. GHD: Twenty adult patients participated in an 18-month randomised, placebo controlled, double blinded study of physiological dose GH substitution, followed by 18 months of open GH treatment. SSR at baseline was reduced in male but not in female GHD patients. Mean SSR (95% confidence interval) for 11 male patients was 89.0 mg/30 minutes (51.9-126.1) as compared to 133.5 mg/30 minutes (59.2-259.9) (P = 0.01) in 24 male controls, and for 11 female patients 48.2 mg/30 minutes (25.9-70.6) as compared to 49.2 mg/30 minutes (12.6-93. 9) in 34 female controls. GH treatment in physiological substitution doses for up to 36 months had no effect on SSR. CONCLUSION: We have demonstrated that longstanding GH hypersecretion in patients with acromegaly induces irreversible changes of sweat gland function, with persistently elevated SSR despite treatment and clinical cure. In GHD patients, SSR was reduced in males but not in females, which together with the established gender difference in normal controls emphasises the role of androgen deficiency as a cofactor for reduced sweating in hypopituitary patients. Sweat gland development seems to be more susceptible to lack of hormones in childhood and adolescence than in adulthood, whereas growth hormone excess can modify sweat function later in life.

Acromegaly↗

Increased urinary albumin excretion rate in breast cancer patients.

A high frequency of slightly increased urinary albumin excretion (UAE) has been reported in patients with malignancies. Earlier studies have indicated a prognostic significance of UAE in some malignant diseases. We measured urinary albumin in 24-h urine samples in 44 patients with newly diagnosed early breast cancer and in 22 patients with relapse of metastatic breast cancer disease. The prevalence of microalbuminuria ( > or = 20 microg/min) was 20.5% in patients with early breast cancer and 54.5% in patients with metastatic disease. Median UAE was significantly higher in patients with metastatic breast cancer compared with the early breast cancer group (20.5 microg/min vs. 9.2 microg/min; p < 0.01). In patients with metastatic breast cancer, univariate survival analysis revealed a significantly lower survival rate in patients with microalbuminuria compared with the normoalbuminuric group (p <0.001). The present study demonstrates a high frequency of microalbuminuria in patients with breast cancer. Increased UAE was most prevalent in patients with metastatic disease. Our results also suggest that UAE may be a prognostic marker in metastatic breast cancer. Further prospective studies with a larger number of patients and controls are needed to test the validity of these observations.

Adult↗

[The clinical impact of gestational diabetes mellitus].

In Denmark, gestational diabetes mellitus (GDM) develops in about 2% of all pregnant women. The discussion of GDM is complicated by lack of consensus regarding screening methods, diagnosis and treatment. Observational studies indicate that untreated GDM is associated with an increased risk of maternal and perinatal morbidity, and that the offspring of GDM mothers tend to be at increased risk of developing diabetes and adiposity as a result of an abnormal intrauterine environment. Several follow-up studies have shown that women with previous GDM run a considerable risk of developing diabetes (especially type 2 diabetes) later in life. Intervention strategies for this high risk group are suggested.

Diabetes, Gestational↗

Clinical significance of urinary albumin excretion in patients with non-Hodgkin's lymphoma.

Slightly increased urinary albumin excretion rates (UAE) have been reported in patients with various types of human cancer. We measured UAE in 24 h urine samples from 48 untreated patients with non-Hodgkin's lymphoma at diagnosis. In patients with a pretreatment UAE >/=20 microgram/min, post-treatment value of UAE was determined following completion of the last treatment. The median UAE was 15.0 microgram/min and the prevalence of microalbuminuria (UAE >/=20 microgram/min) was 39.6%. Increased UAE was significantly associated with Ann Arbor stage, performance status, serum lactate dehydrogenase (LDH) level, and the International Prognostic Index (IPI). The median posttreatment value of UAE was significantly lower than the pretreatment value (P < 0.0001). Our data suggest a clinical and prognostic significance of UAE in patients with non-Hodgkin's lymphoma.

Adolescent↗

[The prognostic value of thrombocytosis in patients with primary lung cancer].

The prognostic information provided by platelet counts was studied in 1115 patients with primary lung cancer and in 550 control patients with benign lung disorders. Patient records were retrospectively reviewed regarding histological tumour type, TNM stage, thromboembolic episodes and survival. The prevalence of thrombocytosis (platelet count > 400 x 10(9)/l) in patients with lung cancer was 32.1% vs. 6.4% in controls (p < 0.0001). Platelet counts increased with TNM stage (p < 0.0001). Patients with thrombocytosis had a shorter survival than patients with normal platelet count (p < 0.0001). Thrombocytosis was a predictor of short survival also when adjusted for tumour type, sex, age, and TNM stage (p < 0.001). The platelet count and the frequency of thrombocytosis declined after tumour resection (p < 0.0001). Thrombocytosis was not associated with thromboembolism. In conclusion, thrombocytosis is a clinically significant prognostic indicator regarding survival in patients with primary lung cancer.

Adult↗

Microalbuminuria in patients with lung cancer.

In a prospective study of 102 outpatients with histologically proven lung cancer, the prevalence and prognostic significance of microalbuminuria (urinary albumin excretion > 20 micrograms/min) were analysed. 65 consecutive outpatients with benign lung disorders served as controls. An immunoturbidimetric assay, sensitive at low concentrations, was used to quantify the albumin excretion rate in timed overnight urine samples. Patients with malignancies had a significantly higher frequency of microalbuminuria (32.4% compared with controls, 13.8%, P < 0.01) and median urinary albumin excretion rate (13.4 versus controls, 8.9 micrograms/min, P < 0.003). Urinary albumin excretion was significantly higher in lung cancer patients with TNM stage III and IV. Patients with malignancies and microalbuminuria had a significantly lower survival rate than patients with normoalbuminuria (probability of survival 1 and 3 years after diagnosis 66% and 16% versus controls, 22% and 4%, P < 0.00001). In a multivariate model, which adjusted for age, sex, performance status, histological type and TNM stage, microalbuminuria continued to be a significant predictor of survival. In conclusion, an increased prevalence of microalbuminuria has been demonstrated in patients with lung cancer. The presence of microalbuminuria was associated with advanced disease stage and poor survival.

Albuminuria↗

Changes in serum concentrations of growth hormone, insulin, insulin-like growth factor and insulin-like growth factor-binding proteins 1 and 3 and urinary growth hormone excretion during the menstrual cycle.

Few studies exist on the physiological changes in the concentrations of growth hormone (GH), insulin-like growth factors (IGF) and IGF-binding proteins (IGFBP) within the menstrual cycle, and some controversy remains. We therefore decided to study the impact of endogenous sex steroids on the GH-IGF-IGFBP axis during the ovulatory menstrual cycle in 10 healthy women (aged 18-40 years). Blood sampling and urinary collection was performed every morning at 0800 h for 32 consecutive days. Every second day the subjects were fasted overnight before blood sampling. Follicle stimulating hormone, luteinizing hormone (LH), oestradiol, progesterone, IGF-I, IGFBP-3, sex hormone-binding globulin, dihydroepiandrosterone sulphate and GH were determined in all samples, whereas insulin and IGFBP-1 were determined in fasted samples only. Serum IGF-I concentrations showed some fluctuation during the menstrual cycle, with significantly higher values in the luteal phase compared to the proliferative phase (P < 0.001). Mean individual variation in IGF-I concentrations throughout the menstrual cycle was 13.2% (SD 4.3; range 0.1-18.3%). There were no cyclic changes in IGFBP-3 serum concentrations and no differences in IGFBP-3 concentrations between the luteal and the proliferative phases. Mean individual variation in IGFBP-3 concentrations throughout the menstrual cycle was 8.8% (SD 2.7; range 3.2-14.1). IGFBP-1 concentrations were inversely associated with insulin concentrations, and showed a significant pre-ovulatory increase that returned to baseline at the day of the LH surge. Fasting insulin concentrations showed large fluctuations throughout the menstrual cycle without any distinct cyclic pattern. No cyclic changes in urinary GH excretion during menstrual cycle were detected. We conclude that, although IGF-I concentrations are dependent on the phase of the menstrual cycle, the variation in IGF-I concentrations throughout the menstrual cycle is relatively small. Therefore, the menstrual cycle does not need to be considered when evaluating IGF-I or IGFBP-3 serum values in women suspected to have GH deficiency.

Adolescent↗

[Kidney function problems in rheumatoid arthritis].

Rheumatoid arthritis is a systemic, disabling disease with significant excess mortality which is partly caused by renal disease, infection and renal insufficiency being the main contributors. The bulk of renal problems in reumatoid arthritis are related to complications such as vasculitis and amyloidosis, and complications to the medical treatment of the disease, the main offenders being gold salts, penicillamine and cyclosporine. Also, there is increasing evidence that reumatoid arthritis per se can cause subclinical renal dysfunction with microalbuminuria as well as clinical disease, caused by immune-complex mediated glomerulonephritis and interstitial tubular fibrosis. In reumatoid arthritis serum creatinine can overestimate renal function by as much as 30% and it is suggested that more sensitive methods such as measuring urinary albumin excretion and glomerular filtration rate should be used for monitoring renal function.

Arthritis, Rheumatoid↗

[Microalbuminuria in rheumatoid arthritis].

To assess the prevalence of microalbuminuria in patients with rheumatoid arthritis and its correlation with disease activity and drug treatment, we studied 65 patients with rheumatoid arthritis and 51 sex and age matched control persons. Microalbuminuria was significantly increased in patients with rheumatoid arthritis (27.7%) as compared to 7.8% in the control group. Patients with microalbuminuria had a significantly greater median duration of disease (11.2 v 7.8 years; p < 0.001). We found a significant correlation to C-reactive protein as a marker for disease activity. Also, a significant association to treatment with gold and penicillamine was found. The measurement of microalbuminuria by immunochemical methods represents a simple and sensitive test to detect subclinical renal damage and may be a sensitive indicator of disease activity in patients with rheumatoid arthritis. We suggest its use in the monitoring of patients with rheumatoid arthritis to detect early subclinical renal dysfunction and drug induced renal damage.

Adult↗

Prognostic significance of thrombocytosis in patients with primary lung cancer.

In patients with malignancies, thrombocytosis has previously been related to disease stage, histological type, and survival. In the present study, the prevalence of thrombocytosis and the prognostic information provided by platelet counts were analysed in a large cohort of patients with primary lung cancer. At the time of diagnosis, pretreatment platelet counts were retrospectively recorded in 1,115 consecutive patients with histologically proven primary lung cancer. All patients were reviewed regarding histological type, tumour, node, metastasis (TNM) classification stage and survival. The prevalence of thrombocytosis in patients with lung cancer was compared with that in a series of 550 consecutive out-patients with benign lung disorders. In 269 surgically resected patients, postoperative platelet counts were recorded 1-3 months after resection of the tumour. In the follow-up period, thromboembolic episodes diagnosed either clinically or at autopsy were recorded. The overall prevalence of thrombocytosis (> 400 x 10(9) platelets.L-1) in the patients with lung cancer was 32%. The frequency of thrombocytosis was significantly higher compared with the control subjects (32 vs 6%; p < 0.0001). Platelet counts differed significantly among subgroups defined by the TNM classification, with the proportion of patients with > 400 x 10(9) platelets.L-1 greatest in the more advanced TNM stages (stage I and II 23% vs stage III and IV 37%; p < 0.0001). Patients with thrombocytosis had a significantly poorer survival than patients with normal platelet counts (p < 0.0001). In a multivariate survival analysis (Cox model), thrombocytosis continued to correlate strongly with poor survival even when adjusted for histological type, sex, age, and TNM stage (p < 0.001). In surgically resected patients, the frequency of preoperative and postoperative thrombocytosis differed significantly (23.0 vs 8.9%; p < 0.0001). Survival rate was significantly reduced in patients with preoperative thrombocytosis (p = 0.005). Thrombocytosis was not associated with an increased incidence of thromboembolism. In conclusion, thrombocytosis is an independent prognostic factor of survival in patients with primary lung cancer. We suggest that platelet counts should be included in future multivariate analyses of survival in patients with lung cancer.

Adult↗

Prevalence and prognostic significance of proteinuria in patients with lung cancer.

The purpose of the present study was to ascertain the prevalence and prognostic significance of proteinuria in patients with lung cancer. Results of urinary dipstick testing were retrospectively reviewed in 1026 consecutive out-patients with histologically proven primary lung cancer and 475 consecutive out-patients with benign pulmonary disorders. Postoperative urinary dipstick test results were recorded in 243 surgically resected patients. Proteinuria was significantly more frequent in patients with lung cancer than in controls (30.1% vs 8.8%, p < 0.0001). The presence of proteinuria was significantly correlated with advanced disease stage (p < 0.0001). The frequency of proteinuria was significantly higher in patients with small cell carcinoma than in patients with other histologic types (p < 0.01). In the surgically resected patients, preoperative and postresection proteinuria occurred in 25.5% and 10.7% respectively (p < 0.0001). Patients with malignancies and proteinuria had significantly poorer survival than patients with normal urinary protein excretion (p < 0.0001). In a multivariate analysis including TNM stage, histologic type, sex, and age, proteinuria continued to be a significant predictor of reduced survival time. Our results suggest a high prevalence of increased urinary protein excretion in patients with primary lung cancer. Proteinuria may also be an independent predictor of poor survival.

Adult↗